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Stat3 regulates genes common to both wound healing and cancer


Wound healing and cancer are both characterized by cell proliferation, remodeling of extracellular matrix, cell invasion and migration, new blood vessel formation, and modulation of blood coagulation. The mechanisms that link wound healing and cancer are poorly understood. We report here that Stat3, a common signaling mechanism involved in oncogenesis and tissue injury, regulates a common set of genes involved in wound healing and cancer. Using oligonucleotide gene arrays and quantitative real-time PCR, we evaluated changes in global gene expression resulting from expression of Stat3 in lung epithelial cells. We report here previously uncharacterized genes induced by Stat3 implicated in signaling pathways common to both wound healing and cancer including cell invasion and migration, angiogenesis, modulation of coagulation, and repression of interferon-inducible genes. Consistent with these results, we found increased Stat3 activity associated with wound healing in chronically inflamed mouse lungs and increased Stat3 activity was identified at the leading edge of lung tumors invading adjacent nontumor stroma. These findings provide a molecular basis for understanding cancer as a deregulation of normal wound healing processes.

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We thank Dr Robert Engleman for assistance with pathological examination of the mouse tissues and Dr Steven Eschrich for review of the microarray analysis. We thank Dr Jacqueline Bromberg for providing Stat3C. We thank Gerold Bepler for critical review of the manuscript, Zhao Chen for statistical advice, and Rebecca Alexander for administrative assistance. This work has been supported in part by the Molecular Imaging Core, Molecular Biology and Sequencing Core, and the DNA Microarray Core at the H Lee Moffitt Cancer Center & Research Institute. This work was partially funded by the Chiles Endowment Biomedical Research Program of the Florida Department of Health (EBH), by a Department of Defense National Functional Genomics Grant (RJ), and by the H Lee Moffitt Cancer Center.

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Correspondence to Eric B Haura.

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Dauer, D., Ferraro, B., Song, L. et al. Stat3 regulates genes common to both wound healing and cancer. Oncogene 24, 3397–3408 (2005).

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  • STAT proteins
  • cancer
  • wound healing
  • Stat3
  • lung cancer

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